Direct prediction of carbapenem resistance in Pseudomonas aeruginosa by whole genome sequencing and metagenomic sequencing

铜绿假单胞菌 碳青霉烯 美罗培南 亚胺培南 基因组 微生物学 生物 基因型 抗生素耐药性 基因 抗生素 细菌 遗传学 医学 肺结核 病理
作者
Bing Liu,Jianpeng Gao,Xue Fei Liu,Guanhua Rao,Jiajie Luo,Han Peng,Weiting Hu,Ze Zhang,Qianqian Zhao,Lizhong Han,Zhi Jiang,Min Zhou
出处
期刊:Journal of Clinical Microbiology [American Society for Microbiology]
卷期号:61 (11) 被引量:6
标识
DOI:10.1128/jcm.00617-23
摘要

ABSTRACT Carbapenem resistance is a major concern in the management of antibiotic-resistant Pseudomonas aeruginosa infections. The direct prediction of carbapenem-resistant phenotype from genotype in P. aeruginosa isolates and clinical samples would promote timely antibiotic therapy. The complex carbapenem resistance mechanism and the high prevalence of variant-driven carbapenem resistance in P. aeruginosa make it challenging to predict the carbapenem-resistant phenotype through the genotype. In this study, using whole genome sequencing (WGS) data of 1,622 P . aeruginosa isolates followed by machine learning, we screened 16 and 31 key gene features associated with imipenem (IPM) and meropenem (MEM) resistance in P. aeruginosa , including oprD(HIGH), and constructed the resistance prediction models. The areas under the curves of the IPM and MEM resistance prediction models were 0.906 and 0.925, respectively. For the direct prediction of carbapenem resistance in P. aeruginosa from clinical samples by the key gene features selected and prediction models constructed, 72 P . aeruginosa -positive sputum samples were collected and sequenced by metagenomic sequencing (MGS) based on next-generation sequencing (NGS) or Oxford Nanopore Technology (ONT). The prediction applicability of MGS based on NGS outperformed that of MGS based on ONT. In 72 P . aeruginosa -positive sputum samples, 65.0% (26/40) of IPM-insensitive and 63.2% (24/38) of MEM-insensitive P. aeruginosa were directly predicted by NGS-based MGS with positive predictive values of 0.897 and 0.889, respectively. By the direct detection of the key gene features associated with carbapenem resistance of P. aeruginosa , the carbapenem resistance of P. aeruginosa could be directly predicted from cultured isolates by WGS or from clinical samples by NGS-based MGS, which could assist the timely treatment and surveillance of carbapenem-resistant P. aeruginosa .
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